title: A study of the combination of triamcinolone and 5-fluorouracil in modulating keloid fibroblasts in vitro.
abstract: BACKGROUND
  Preliminary clinical trials suggest a superior effect when steroids and 5-fluorouracil are injected together for the intralesional therapy of keloids. In addition, it has been proposed that low-dose 5-fluorouracil may have advantages over conventional high dosages. We explored the molecular basis for the potential synergy involved in the combined treatment with triamcinolone and 5-fluorouracil.
  
  
  METHODS
  The effects of triamcinolone alone or in combination with low-dose 5-fluorouracil on cell proliferation, cell-cycle progression, apoptosis and regulation of p53, p21, type I collagen (Col-1), vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1) and matrix metalloproteinase-2 (MMP-2) production in primary cultured keloid fibroblasts were examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), flow cytometric and Western blotting assays.
  
  
  RESULTS
  Triamcinolone suppressed cell proliferation and induced G1 cell-cycle arrest but not apoptosis. By contrast, 5-fluorouracil induced G2 cell-cycle arrest and apoptosis that may be associated with p53 activation and p21 up-regulation. The modulation of Col-1, VEGF, TGF-beta1 and MMP-2 expression by triamcinolone and 5-fluorouracil alone or their combination varied between individual cell lines; the trend is to promote a reduction in Col-1 and TGF-beta1 but up-regulation of MMP-2 expression. 5-Fluorouracil played a predominant role in the combined treatment leading to more significant cell proliferation inhibition, apoptosis, Col-1 suppression and MMP-2 induction (p < 0.05).
  
  
  CONCLUSIONS
  Our data provide the molecular-based evidence for the observed clinical benefits of adding 5-fluorouracil to a steroid injection for improved scar regression and reduced recurrence of keloids. We expect fewer undesirable side effects in the combined treatment when the lower therapeutic dose of the individual drugs is to be used.
authors.affiliation: Division of Plastic, Reconstructive and Aesthetic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.forename: Yi J
authors.initials: YJ
authors.lastname: Cai
authors.forename: Ivan
authors.initials: I
authors.lastname: Lung
authors.forename: Billy C S
authors.initials: BC
authors.lastname: Leung
authors.forename: Andrew
authors.initials: A
authors.lastname: Burd
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007627:Keloid / Q000188:drug therapy* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D012680:Sensitivity and Specificity; D014221:Triamcinolone / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D014221:Triamcinolone; D020778:Matrix Metalloproteinase 2; D005472:Fluorouracil
keywords: 5-Fluorouracil; Fibroblast; Keloid; Triamcinolone